We discovered a highly potent bicyclic cage-like conformationally restricted, and proteolytically stable cyclopeptide, termed sunflower derived trypsin inhibitor, SFTI-1. We designed and synthesized a number of SFTI-1 analogs to improve its inhibitory specificity and serum stability. Some of the conformationally constrained cage-like bicyclic peptides and peptidomimetics demonstrate much better selectivity (more than 20-fold improvement) and stability. Our current goals are to develop more selective inhibitory analogs to SFTI-1, and to evaluate them in in vivo systems.